New horizons for treating castration resistant prostate cancer: Bipolar Androgen Therapy

ABSTRACT

The treatment of metastatic prostate cancer has evolved over the decades focusing on manipulation of the androgen receptor pathway with or without chemotherapy. Despite new drugs discovered with incrementing survival benefits, the disease continues to be fatal after development of castration resistance and progression on abiraterone and enzalutamide. In this context, attempts of androgen pathway manipulation have led to the development of the Bipolar Androgen Therapy (BAT), which consists of a rapid transition from a castration state to supraphysiologic levels of testosterone and then back to castration levels. Pilot studies have shown this strategy to be safe and supported the development of further clinical trials. Phase II trials have demonstrated PSA response and disease control in a significant number of patients, including a possible resensitizing effect to enzalutamide. This promising strategy may in the future become another available option for these patients.

RESUMO

O tratamento do câncer de próstata metastático tem evoluído ao longo das décadas focando na manipulação da via do receptor de andrógeno, com ou sem quimioterapia. Apesar das novas drogas descobertas com incremento dos benefícios de sobrevivência, a doença continua a ser fatal após o desenvolvimento da resistência à castração e à progressão da abiraterona e da enzalutamida. Neste contexto, tentativas de manipulação de vias androgênicas levaram ao desenvolvimento da Terapia Bipolar de Andrógênos (BAT), que consiste em uma transição rápida de um estado de castração para níveis suprafisiológicos de testosterona e depois de volta aos níveis de castração. Estudos piloto mostraram que esta estratégia é segura e apoiaram o desenvolvimento de novos ensaios clínicos. Ensaios de Fase II demonstraram resposta do PSA e controle da doença em um número significativo de pacientes, incluindo um possível efeito de ressensibilização à enzalutamida. Essa estratégia promissora pode, no futuro, tornar-se outra opção disponível para esses pacientes.

Keywords:

Prostatic Neoplasm - Castration-Resistant - Testosterone - Prostate-Specific Antigen

Descritores:

Neoplasias da Próstata - Resistente à Castração - Testosterona - Antígeno Prostático Específico

Publikationsverlauf

Eingereicht: 23. Juli 2018

Angenommen: 01. Oktober 2018

Artikel online veröffentlicht:
26. Februar 2025

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